Types of EMT.

EMT - epithelial to mesenchymal transition

- Classification of EMT into three groups.
Type 1 Type 2 Type 3
Type 1 EMT during embryogenesis
one example of many type 1 EMT that occur during embryogenesis

• A zygote undergoes embryonic development –

gastrulation.
Primitive
streak Epiblast
• These epiblast cells produce E-
cadherin and show signs of apical basal
polarity.

• These “epithelial” cells migrate through the

primitive streak to produce the mesoderm cells
(germ line cells).

• These cell show enhanced migratory capacity in Migrating

comparison to epiblast cells.
cells
Type 1 EMT during embryogenesis
Process of EMT during embryogenesis

• This process is driven by the canonical Wnt

signalling pathway.

• TGF-β signalling mediate the actions of Wnt.

• Snail, Eomes and Mesps transcription factors

drive EMT during embryogenesis
Type 1 EMT during embryogenesis
Transcription factors driving EMT

• Snail is responsible for a range of different gene expression changes.

Type 2 EMT during Fibrosis
Type 2 EMT – one example of many – injury to the kidney.

• Organ fibrosis – the formation of excess fibrous connective tissue – is

mediated by inflammatory cells and fibroblasts.
• As well as components of the ECM – laminins!

• Injury to the kidney – the damage cells will release histamine,

bradykinin, and prostaglandins this will induce an inflammatory
response.

• This recruits macrophages and activated fibroblasts that release growth

factors.
Type 2 EMT during fibrosis
Process of EMT during organ fibrosis

• Growth factors released are

typically TGF-β, PDGF, EGF and
FGF.
• TGF-β initiates ECM production
• FGF stimulates angiogenesis and
proliferation of fibroblasts.

• Metallopeptidase enzymes are

also released – MMP2, 3 and 9.
TGF-β induced EMT is associated with a loss of E-cadherin.
Type 3 EMT – Cancer progression
• A tumour and a cancer cell are defined as having uncontrolled
proliferation and initiation of angiogenesis.

• A cancerous cell however has the ability to migrate (metastasise)

whereas a benign tumour cannot.

• The cancer cell will have the potential to metastasise as it has/is going
through EMT.
Type 3 EMT – Cancer progression

• The acquisition of metastatic potential is uncertain.

• It can be suggested that the genetic alterations (mutations) or signalling is
responsible for the progression through EMT. It is likely both.

• The tumour associated stroma releases growth factors, these are

similar to those produced in type 2 EMT. The EMT process has been
hijacked by the cancer.

• TGF-β, PDGF, EGF and HGF.

Type 3 EMT – Cancer progression
• Once the cancer has gain the ability
invade and regulate the ECM it can
invade through the basement
membrane.

• Through the process of intravasation the

cancer cell can enter the blood vessel.

• In reverse, so, extravasation and invasion

into a distant site is where MET occurs.
Theories
• What we do know.
• The likelihood of where the cancer may spread to from it’s original site
• What we don’t know.
• How this happens – current theory is seed and soil.

• Seed and soil vs blood flow theory

• Both partially correct – if a tumour metastases through the lymphatic system the
likelihood is MET will occur in the closest lymph node.
• If the cell spreads through the blood it follow that seed and soil theory the
anatomy of the new site has some importance.